title: Seropositivity to cytomegalovirus, inflammation, all-cause and cardiovascular disease-related mortality in the United States.
abstract: BACKGROUND
  Studies have suggested that CMV infection may influence cardiovascular disease (CVD) risk and mortality. However, there have been no large-scale examinations of these relationships among demographically diverse populations. The inflammatory marker C-reactive protein (CRP) is also linked with CVD outcomes and mortality and may play an important role in the pathway between CMV and mortality. We utilized a U.S. nationally representative study to examine whether CMV infection is associated with all-cause and CVD-related mortality. We also assessed whether CRP level mediated or modified these relationships.
  
  
  RESULTS
  Data come from subjects ≥ 25 years of age who were tested for CMV and CRP level and were eligible for mortality follow-up on December 31(st), 2006 (N = 14153) in the National Health and Nutrition Examination Survey (NHANES) III (1988-1994). Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for all-cause and CVD-related mortality by CMV serostatus. After adjusting for multiple confounders, CMV seropositivity remained statistically significantly associated with all-cause mortality (HR 1.19, 95% CI: 1.01, 1.41). The association between CMV and CVD-related mortality did not achieve statistical significance after confounder adjustment. CRP did not mediate these associations. However, CMV seropositive individuals with high CRP levels showed a 30.1% higher risk for all-cause mortality and 29.5% higher risk for CVD-related mortality compared to CMV seropositive individuals with low CRP levels.
  
  
  CONCLUSIONS
  CMV was associated with a significant increased risk for all-cause mortality and CMV seropositive subjects who also had high CRP levels were at substantially higher risk for both for all-cause and CVD-related mortality than subjects with low CRP levels. Future work should target the mechanisms by which CMV infection and low-level inflammation interact to yield significant impact on mortality.
authors.affiliation: Department of Epidemiology, Center for Social Epidemiology and Population Health, School of Public Health, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Simanek
authors.forename: Jennifer Beam
authors.initials: JB
authors.lastname: Dowd
authors.forename: Graham
authors.initials: G
authors.lastname: Pawelec
authors.forename: David
authors.initials: D
authors.lastname: Melzer
authors.forename: Ambarish
authors.initials: A
authors.lastname: Dutta
authors.forename: Allison E
authors.initials: AE
authors.lastname: Aiello
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology / Q000209:etiology / Q000401:mortality*; D002423:Cause of Death; D003587:Cytomegalovirus / Q000302:isolation & purification / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000097:blood / Q000150:complications / Q000453:epidemiology* / Q000401:mortality; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications / Q000453:epidemiology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009749:Nutrition Surveys; D016036:Seroepidemiologic Studies; D014481:United States / Q000453:epidemiology